U.S. patent application number 12/117001 was filed with the patent office on 2009-07-16 for labeled molecule for prognosing tumor grade of head neck cancer and method for the same.
Invention is credited to Joseph T. Chang, Ann-Joy CHENG, Ching-Chi Chiu.
Application Number | 20090181472 12/117001 |
Document ID | / |
Family ID | 40850990 |
Filed Date | 2009-07-16 |
United States Patent
Application |
20090181472 |
Kind Code |
A1 |
CHENG; Ann-Joy ; et
al. |
July 16, 2009 |
LABELED MOLECULE FOR PROGNOSING TUMOR GRADE OF HEAD NECK CANCER AND
METHOD FOR THE SAME
Abstract
The present invention discloses a labeled molecule for
prognosing the tumor grade of head neck cancer and a method for the
same, wherein a 78-kDA glucose regulated protein (GRP78) is adopted
as a labeled molecule of head neck cancer. GRP78 is much more
overexpressed in head neck cancer cells than in non-cancer cells.
GRP78 also has relation with tumor size, tumor depth and tumor
metastasis. Therefore, the present invention uses GRP78
overexpression as a reference for tumor grading of head neck
cancer.
Inventors: |
CHENG; Ann-Joy; (Linkou
Shiang, TW) ; Chang; Joseph T.; (Linkou Shiang,
TW) ; Chiu; Ching-Chi; (Daliao Shiang, TW) |
Correspondence
Address: |
SINORICA, LLC
2275 Research Blvd., Suite 500
ROCKVILLE
MD
20850
US
|
Family ID: |
40850990 |
Appl. No.: |
12/117001 |
Filed: |
May 8, 2008 |
Current U.S.
Class: |
436/516 |
Current CPC
Class: |
G01N 2333/47 20130101;
G01N 33/57407 20130101 |
Class at
Publication: |
436/516 |
International
Class: |
G01N 33/561 20060101
G01N033/561 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 11, 2008 |
TW |
97101258 |
Claims
1. A labeled molecule for prognosing a tumor grade of head neck
cancer, characterized in comprising a 78-kDA glucose regulated
protein (GRP78), wherein an expression of said 78-kDA glucose
regulated protein in a head neck cancer tissue relative to an
expression of a normal tissue is used to prognose a tumor grade of
said head neck cancer.
2. The labeled molecule for prognosing a tumor grade of a head neck
cancer according to claim 1, wherein said expression of said 78-kDA
glucose regulated protein in said head neck cancer tissue relative
to said expression of said normal tissue has a positive correlation
with said tumor grade of said head neck cancer.
3. The labeled molecule for prognosing a tumor grade of head neck
cancer according to claim 1, wherein said tumor grade of said head
neck cancer includes factors of tumor size, tumor depth and tumor
metastasis to nymph nodes.
4. A method for prognosing a tumor grade of head neck cancer,
characterized in using a 78-kDA glucose regulated protein (GRP78)
as a labeled molecule of a head neck cancer, wherein an expression
of said 78-kDA glucose regulated protein in said head neck cancer
tissue relative to an expression of a normal tissue is used to
prognose a tumor grade of said head neck cancer.
5. The method for prognosing a tumor grade of head neck cancer
according to claim 4, wherein said expression of said 78-kDA
glucose regulated protein in said head neck cancer tissue relative
to said expression of said normal tissue has a positive correlation
with said tumor grade of said head neck cancer.
6. The method for prognosing a tumor grade of head neck cancer
according to claim 4, wherein said tumor grade of said head neck
cancer includes factors of tumor size, tumor depth and tumor
metastasis to nymph nodes.
7. The method for prognosing a tumor grade of head neck cancer
according to claim 4, wherein a protein analysis is used to detect
said expression of said 78-kDA glucose regulated protein in said
head neck cancer tissue relative to said expression of said normal
tissue.
8. The method for prognosing a tumor grade of head neck cancer
according to claim 7, wherein a western blot analysis method is
used to perform said protein analysis of said 78-kDA glucose
regulated protein in said head neck cancer tissue and said normal
tissue.
Description
BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention relates to an application of a 78-kDA
glucose regulated protein (GRP78), particularly to a
GRP78-containing labeled molecule for prognosing the tumor grade of
head neck cancer and a method for the same.
[0003] 2. Description of the Related Art
[0004] The 78-kDA glucose regulated protein (GRP78), also known as
hsp70-5, hspA5 or Bip, is one member of the heat shock protein 70
(HSP70) family. GRP78 is a functional protein, which implements
folding up a newly-synthesized protein to have an appropriate
conformation in the endoplasmic reticulum. According to previous
researches, a crisis of cells, such as a hypoxia state or an
ultraviolet radiation, will trigger GRP78 to assist in the
degradation of the incorrectly folded protein. Therefore, GRP78 is
thought to be a stress sensor of the endoplasmic reticulum, which
functions as the cyto-protection and anti-apoptosis mechanisms of
cells.
[0005] It is also found in some researches that GRP78 can function
as the labeled protein of breast cancer. GRP78 can help cells
survive in a glucose-deficiency environment. Some researches show:
a patient having overexpressed GRP78 has a higher recurrence rate
no matter in what stage of cancer. Therefore, it is thought that
GRP78 helps breast cancer cells resist against chemotherapy. This
finding gives physicians a very important therapeutic reference,
and unnecessary medicine and useless therapy can thus be avoided if
GRP78 concentration is tested before chemotherapy.
[0006] At present, none labeled molecule can be clinically used to
determine the tumor grade of head and neck cancer, nor is molecular
medicine for an overexpressed gene designed to cure head neck
cancer. In fact, the current technology is still indefinite about
whether GRP78 can be used in tumor grading.
BRIEF DESCRIPTION OF THE DRAWING
[0007] The patent or application file contains at least one drawing
executed in color. Copies of this patent or patent application
publication with color drawing(s) will be provided by the office
upon request and payment of the necessary fee.
[0008] FIG. 1 is a diagram of electrophoregrams showing that GRP78
is overexpressed in cancer tissues.
SUMMARY OF THE INVENTION
[0009] The primary objective of the present invention is to provide
a labeled molecule for prognosing the tumor grade of head neck
cancer and a method for the same, wherein a 78-kDA glucose
regulated protein (GRP78) is used to estimate the tumor grade of
head neck cancer, whereby physicians can adopt proper measures to
promote the therapeutic effect of head neck cancer.
[0010] The present invention is based on the facts that GRP78
expression in head neck cancer cells is much higher than the
expression in non-cancer cells and that GRP78 expression correlates
with clinical malignant indications, such as tumor size, tumor
depth, lymph metastasis, etc., wherein the abovementioned facts are
obtained via analyzing the relative GRP78 expression in head neck
cancer tissue and normal tissue. Thus, the present invention adopts
GRP78 as a labeled molecule for prognosing the tumor grade of head
neck cancer.
[0011] Below, detailed description, in cooperation with the
drawing, is used to further demonstrate the objectives,
characteristics and efficacies of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0012] The present invention adopts GRP78 as a labeled molecule for
head neck cancer, which is clinically related with head neck cancer
and overexpressed in head neck cancer. Below, clinical experiments
will be analyzed to verify the theory and efficacies of the present
invention.
[0013] In the present invention, cancer tissues of head neck cancer
patients (Patients A-F) are compared with normal tissues. A protein
analysis is used to detect GRP78 expressions in head neck cancer
tissues and normal tissues, and a western blot analysis method is
used to perform the protein analysis. Refer to FIG. 1. GRP78 is
overexpressed on the electrophoregrams of the head neck cancer
specimens, wherein N denotes a normal tissue, and T denotes a
cancer tissue. A cytoskeleton protein (Actin) is used in the
control groups. It is found in FIG. 1: GRP78 is overexpressed in
the cancer tissue of a patient no matter in protein or RNA
(ribonucleic acid).
[0014] Table. 1 shows the characteristics of the research subjects.
The subjects include: 54 males (91.5%) and 5 females (8.5%). The
ages range from 29 to 77 years old with a mean of 49. Among them,
37 persons are habituated to alcohol, and 51 persons are habituated
to cigarette, and 53 persons are habituated to areca. About 80% of
patients have the habit of alcohol drinking, cigarette smoking or
areca chewing. Among 56 pairs of specimens, GRP78 is overexpressed
in the cancer tissues of 34 patients; the ratio of GRP78
overexpression is as high as 61%.
TABLE-US-00001 TABLE 1 Count of persons (59 persons Characteristics
totally) Percentage Sex Male 54 91.5% Female 5 8.5% Age <40
years old 12 20.3% 40-50 years old 21 35.6% 51-60 years old 15
25.5% 61-70 years old 8 13.5% >70 years old 3 5.1% Addiction
Alcohol 37 62.7% Cigarette 51 86.4% Areca 53 89.8%
[0015] Table. 2 shows the clinical statistics about GRP78
overexpression and pathological characteristics. It is found in
Table. 2: GRP78 overexpression has statistical correlations with T
stage (P=0.035), N stage (P=0.01), overall stage (P=0.034), tumor
depth (P=0.035) and extracapsular spread in lymph nodes (P=0.036).
The correlations between GRP78 overexpression and tumor area, tumor
stage and tumor depth indicate that GRP78 has relation with the
growth of cancer cells. The correlations between GRP78
overexpression and metastasis to lymph nodes and extracapsular
spread in lymph nodes indicate that GRP78 has relation with the
metastasis of cancer cells. Thus, it is clinically proved that
GRP78 participates in the growth and metastasis of cancer cells.
Therefore, the present invention uses the molecule GRP78 in
clinically prognosing the tumor grade of head neck cancer.
TABLE-US-00002 TABLE 2 GRP78 overexpression (%) Parameters N No Yes
P value T stage T1-t2 30 14 (47) 16 (53) 0.035 T3-t4 29 6 (21) 23
(79) N stage N = 0 44 19 (43) 25 (57) 0.010 N > 0 15 1 (7) 14
(93) Overall stage I-II 27 13 (48) 14 (52) 0.034 III-IV 32 7 (22)
25 (78) Differentiation Benignant 24 8 (33) 16 (67) 0.939 *m-p 35
12 (34) 23 (66) Tumor depth <10 mm 30 14 (47) 16 (53) 0.035
>10 mm 29 6 (21) 23 (79) Extracapsular No 47 19 (40) 28 (60)
0.036 spread in lymph Yes 12 1 (8) 11 (92) nodes Sum 59 20 39 (66)
*m-p: moderate to poor
[0016] Those described above are only to exemplify the present
invention but not to limit the scope of the present invention. Any
modification or variation according to the spirit of the present
invention is to be also included within the scope of the present
invention, which is based on the claims stated below.
* * * * *